The major goal of these studies is to develop markers predictive of which ductal carcinoma in situ (DCIS) cases will recur and/or become invasive to aid in the clinical management of mammographically-detected DCIS. To do this we will examine cases of pure DCIS and DCIS associated with invasive cancers for a number of molecular and immunohistochemical markers known to be abnormal in invasive cancers. Included among the markers to be evaluated are loss of heterozygosity (LOH) and gene amplification at various chromosomal loci, various immunohistochemical markers associated with invasion as well as markers associated with dysregulated proliferation and apoptosis. A second goal is to undertake preliminary studies to identify molecular markers in nonmalignant epithelium that might distinguish those cases likely to progress to cancer. These studies will concentrate on characterizing the morphologically nonmalignant mammary epithelium adjacent to malignancies, comparing this tissue to truly normal mammary epithelium and to other tissues of the patient (i.e., skin vs. mammary epithelium). If these studies are successful in identifying molecular aberrations in nonmalignant epithelium adjacent to malignancy, future studies beyond the scope of the proposal could evaluate marker efficacy for early diagnosis when used in combination with other diagnostic modalities such as needle aspirates and/or random nipple biopsies. Additionally, such markers mabe surrogates in chemoprevention trials for the currently used endpoint of malignancy which would allow trials to be performed with fewer patients and over shorter time periods.